Abstract
Summary: Three decades after the first description of glutaryl-CoA dehydrogenase deficiency, major progress has been achieved in the prevention of acute striatal necrosis and neurological sequelae in affected children, if diagnosis is made early and treatment is started before manifestation of acute encephalopathic crises. However, all concepts for diagnostic work-up, monitoring, and treatment are solely experience-based, and 10–35% of early-diagnosed children do not or only incompletely benefit from the current management. They still develop neurological deterioriation and sequelae despite early implementation of dietary treatment, carnitine supplementation and emergency treatment during acute intercurrent illnesses. International efforts should be made to move management of affected children from experience-based to evidence-based medicine. Major tools for this optimization are the establishment of an international patients' database, the implementation of an international prospective clinical study, and the development of international guidelines for diagnostic work-up, monitoring and therapy.
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REFERENCES
Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellscha ten (AWMF) (URL:http://www.uni-duesseldorf.de/WWW/AWMF/ll/llmanual.htm)
B hr O, Mader I, Zschocke J,et al (2002)Adult onset glutaric aciduria type I presenting with leukoencephalopathy.Neurology 59:1802-1804.
Baric I, Wagner L, Feyh P,et al (1999)Sensitivity and specificity o ree and total glutaric and 3-hydroxyglutaric acids measurements by stable isotope dilution assays for the diagnosis o glutaric aciduria type I.J Inherit Metab Dis 22:867-881.
Bjugstad KB, Goodman SI, Freed CR (2000)Age at symptomonset predicts severity o motor impairment and clinical outcome o glutaric acidemia type I.J Pediatr 137:681-686.
Busquets C, Merinero B, Christensen E,et al (2000)Glutaryl-CoA dehydrogenase deficiency in Spain:evidence o two groups o patients,genetically,and biochemically distinct.Pediatr Res 48:315-322.
Christensen E (1993)Afibroblast glutaryl-CoA dehydrogenase assay using detritiation of 3 H-labelled glutaryl-CoA:application in the genotyping o the glutaryl-CoA dehydrogenase locus.Clim Chim Acta 220:71-80.
Goodman SI, Markey SP, Moe PG,et al (1975)Glutaric aciduria:a ''new ''disorder o amino acid metabolism.Biochem Med 12:12-21.
Goodman SI, Stein DE, Schlesinger S,et al (1998)Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I):review and report o thirty novel mutations.Hum Mutat 12: 141-144.
Greenberg CR, Prasad AN, Dilling LA,et al (2002)Outcome of thefirst 3-years of a DNA-based neonatal screening program or glutaric acidemia type I in Manitoba and northwestern Ontario,Canada.Mol Genet Metab 75:70-78.
Hoffmann GF, Athanassopoulos S, Burlina AB,et al (1996)Clinical course,early diagnosis, treatment,and prevention o disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics 27:115-123.
Koeller DM, Woontner M, Crnic LS,et al (2002)Biochemical,pathologic and behavioral analysis o a mouse model o glutaric acidemia type I.Hum Mol Genet 11:347-357.
Kölker S, Ramaekers V, Zschocke J, Hoffmann GF (2001)Acute encephalopathy despite early therapy in a patient with homozygosity or E365K in the glutaryl-coenzyme A dehydrogenase gene.J Pediatr 138:277-279.
Kölker S, Greenberg CR, Mffller E, Naughten ER, Hoffmann GF (2004a)Emergency treat-ment in glutaryl-CoA dehydrogenase deficiency.J Inherit Metab Dis 27:893902.
Kölker S, Koeller DM, Sauer S,et al (2004b)Excitotoxicity and bioenergetics in glutaryl-CoA dehydrogenase deficiency.J Inheri tMetab Dis 27:805812.
Kyllerman M, Skjeldal O, Christensen E,et al (2004)Long-term ollow-up,neurological out-come and survival rate in 28 Nordic patients with glutaric aciduria type 1.Eur J Paediatr Neurol 8:121-129.
Lindner M, Kölker S, Schulze A, Christensen E, Greenberg CR, Hoffmann GF (2004) Neonatal screening or glutaryl-CoA dehydrogenase deficiency.J Inherit Metab Dis 27: 851-859.
Monavari AA, Naughten ER (2000)Prevention of cerebral palsy in glutaric aciduria type I by dietary management.Arch Dis Child 82:67-70.
Mühlhausen C, Hoffmann GF, Strauss KA,et al (2004)Maintenance treatment o glutaryl-CoA dehydrogenase deficiency.J Inherit Metab Dis 27:885-892.
National Institute or Clinical Excellence (NICE).(URL:http://www.nice.org.uk/ Cat.asp?pn =professional & cn =toplevel & ln =en)
Neumaier-Probst E, Harting I, Seitz A, Ding C, Kölker S (2004)Neuroradiologicalfindings in glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency).J Inherit Metab Dis 27: 869-876.
Scottish Intercollegiate Guidelines Network (SIGN).(URL:http://www.sign.ac.uk/ guidelines/fulltext/50/index.html)
Strauss KA, Puffenberger EG, Robinson DL, Morton DH (2003)Type I glutaric aciduria, part 1:Natural history of 77 patients.Am J Med Genet 121C:38-52.
Yannicelli S, Rohr F, Warman M(1994)Nutrition support or glutaric acidemia type I.J Am Diet Assoc 94:183-191.
Zschocke J, Quak E, Guldberg P, Hoffmann GF (2000)Mutation analysis in glutaric aciduria type I.J Med Genet 37:177-181.
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KÖlker, S., Burgard, P., Okun, J.G. et al. Looking forward—An evidence-based approach to glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis 27, 921–926 (2004). https://doi.org/10.1023/B:BOLI.0000045778.73581.7d
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DOI: https://doi.org/10.1023/B:BOLI.0000045778.73581.7d